2b4r: Difference between revisions

Revision as of 17:34, 21 February 2008

Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from Plasmodium falciparum at 2.25 Angstrom Resolution reveals intriguing extra electron density in the active site

OverviewOverview

The crystal structure of D-glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH) from the major malaria parasite Plasmodium falciparum is solved at 2.25 A resolution. The structure of PfGAPDH is of interest due to the dependence of the malaria parasite in infected human erythrocytes on the glycolytic pathway for its energy generation. Recent evidence suggests that PfGAPDH may also be required for other critical activities such as apical complex formation. The cofactor NAD(+) is bound to all four subunits of the tetrameric enzyme displaying excellent electron densities. In addition, in all four subunits a completely unexpected large island of extra electron density in the active site is observed, approaching closely the nicotinamide ribose of the NAD(+). This density is most likely the protease inhibitor AEBSF, found in maps from two different crystals. This putative AEBSF molecule is positioned in a crucial location and hence our structure, with expected and unexpected ligands bound, can be of assistance in lead development and design of novel antimalarials.

About this StructureAbout this Structure

2B4R is a Single protein structure of sequence from Plasmodium falciparum with , and as ligands. This structure supersedes the now removed PDB entry 1ZYA. Active as Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating), with EC number 1.2.1.12 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from Plasmodium falciparum at 2.25 A resolution reveals intriguing extra electron density in the active site., Robien MA, Bosch J, Buckner FS, Van Voorhis WC, Worthey EA, Myler P, Mehlin C, Boni EE, Kalyuzhniy O, Anderson L, Lauricella A, Gulde S, Luft JR, DeTitta G, Caruthers JM, Hodgson KO, Soltis M, Zucker F, Verlinde CL, Merritt EA, Schoenfeld LW, Hol WG, Proteins. 2006 Mar 15;62(3):570-7. PMID:16345073

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-[[Image:2b4r.gif|left|200px]]<br /><applet load="2b4r" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2b4r.gif|left|200px]]<br /><applet load="2b4r" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2b4r, resolution 2.25&Aring;" />
 '''Crystal structure of glyceraldehyde-3-phosphate dehydrogenase from Plasmodium falciparum at 2.25 Angstrom Resolution reveals intriguing extra electron density in the active site'''<br />
 ==Overview==
-The crystal structure of D-glyceraldehyde-3-phosphate dehydrogenase, (PfGAPDH) from the major malaria parasite Plasmodium falciparum is solved, at 2.25 A resolution. The structure of PfGAPDH is of interest due to the, dependence of the malaria parasite in infected human erythrocytes on the, glycolytic pathway for its energy generation. Recent evidence suggests, that PfGAPDH may also be required for other critical activities such as, apical complex formation. The cofactor NAD(+) is bound to all four, subunits of the tetrameric enzyme displaying excellent electron densities., In addition, in all four subunits a completely unexpected large island of, extra electron density in the active site is observed, approaching closely, the nicotinamide ribose of the NAD(+). This density is most likely the, protease inhibitor AEBSF, found in maps from two different crystals. This, putative AEBSF molecule is positioned in a crucial location and hence our, structure, with expected and unexpected ligands bound, can be of, assistance in lead development and design of novel antimalarials.
+The crystal structure of D-glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH) from the major malaria parasite Plasmodium falciparum is solved at 2.25 A resolution. The structure of PfGAPDH is of interest due to the dependence of the malaria parasite in infected human erythrocytes on the glycolytic pathway for its energy generation. Recent evidence suggests that PfGAPDH may also be required for other critical activities such as apical complex formation. The cofactor NAD(+) is bound to all four subunits of the tetrameric enzyme displaying excellent electron densities. In addition, in all four subunits a completely unexpected large island of extra electron density in the active site is observed, approaching closely the nicotinamide ribose of the NAD(+). This density is most likely the protease inhibitor AEBSF, found in maps from two different crystals. This putative AEBSF molecule is positioned in a crucial location and hence our structure, with expected and unexpected ligands bound, can be of assistance in lead development and design of novel antimalarials.
 ==About this Structure==
-B4R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with NAD, AES and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. This structure superseeds the now removed PDB entry 1ZYA. Active as [http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2B4R OCA].
+B4R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum] with <scene name='pdbligand=NAD:'>NAD</scene>, <scene name='pdbligand=AES:'>AES</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1ZYA. Active as [http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B4R OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Single protein]]
 [[Category: Bosch, J.]]
-[[Category: Hol, W.G.J.]]
+[[Category: Hol, W G.J.]]
-[[Category: Robien, M.A.]]
+[[Category: Robien, M A.]]
-[[Category: SGPP, Structural.Genomics.of.Pathogenic.Protozoa.Consortium.]]
+[[Category: SGPP, Structural Genomics of Pathogenic Protozoa Consortium.]]
 [[Category: AES]]
 [[Category: GOL]]
@@ Line 29: / Line 29: @@
 [[Category: structural genomics of pathogenic protozoa consortium]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 25 08:53:12 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:34:09 2008''